© 2015 Society for Vascular Surgery. Objective This study compared the performance of the Aorfix endograft (Lombard Medical, Oxfordshire, United Kingdom) in standard (<60°), highly angled (60°-90°), and severely angled (>90°) aortic necks in the PYTHAGORAS study and evaluated changes in neck morphology over time. Methods PYTHAGORAS is a prospective nonrandomized clinical trial of the Aorfix endograft. We divided the endovascular aneurysm repair (EVAR) cohort into groups by standard, high, and severe neck angle. The primary control group was patients concurrently undergoing open repair. Mortality at 30 days, 1 year, and 2 years and 30-day freedom from Society for Vascular Surgery major adverse events for the EVAR groups was compared with the open control. Aneurysm sac change, type I and III endoleaks, graft migration, and the reintervention rate at 1 and 2 years was compared between the standard, highly, and severely angled populations. The relative risk of graft complications with a neck diameter increase >10% was also calculated. At predetermined anatomic points, the effect of oversizing on aortic diameter was evaluated by calculating oversize percentage ([1 - outer aortic diameter measured at a given time/stent graft diameter] × 100%) preoperatively and at 3 years. In addition, the average oversizing percentage at 30 days and annually at 1 to 5 years was compared with the preoperative oversizing percentage. Finally, complication rates with â‰¥30% vs <30% planned oversizing were compared. Results The adverse event rate was lower for every EVAR group than the open control. In addition, the mortality rates at 30 days, 1 year, and 2 years were similar between the standard-angle (1.5%, 3.0%, 4.5%), high-angle (0.9%, 7.3%, 13.8%), and severe-angle (4.8%, 9.5%, 14.3%) EVAR groups and the open control groups (1.3, 6.6%, 10.5%). At 1 and 2 years, there was no difference in graft complications among the EVAR groups. However, with neck dilatation of >10% at 5 mm above the proximal renal and 1 mm below the distal renal, there was an increased risk of graft migration (relative risk, 4.38 [P =.01] and 4.33 [P =.002], respectively). For all predetermined anatomic points, the oversizing percentage decreased over time. The rate of oversize percentage decrease was faster at more distal aortic locations, reaching <10% at 30 days 15 mm below the renal, at 2 years 7 mm below the renal, and at 5 years 1 mm below the renal (P <.001 for all). Half the oversize percentage achieved at the index procedure remained at 3 years (Pearson correlation coefficient = 0.5). However, there was no difference in complications between the 30% and <30% planned oversize groups. Conclusions The Aorfix endograft has performed well in excluding aneurysms with standard and highly angled aortic neck anatomy.